case report ovarian hyperstimulation syndrome, the master of...

Case ReportOvarian Hyperstimulation Syndrome, the Master of Disguise?

Emily Charlotte Ironside and Andrew James Hotchen

Oxford University Hospitals, Headley Way, Headington, Oxford OX3 9DU, UK

Correspondence should be addressed to Andrew James Hotchen; [email protected]

Received 20 July 2014; Revised 12 January 2015; Accepted 19 January 2015

Academic Editor: Yuh-Feng Wang

Copyright © 2015 E. C. Ironside and A. J. Hotchen. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The use of IVF has risen dramatically over the past 10 years and with this the complications of such treatments have also risen.One such complication is ovarian hyperstimulation syndrome with which patients can present acutely to hospital with shortness ofbreath. On admission, a series of blood tests are routinely performed, including the d-dimer.We present a case of a 41-year-old ladywho had recently undergone IVF and presented with chest pain and dyspnoea. In the emergency department, a d-dimer returnedas mildly elevated. Consequential admission onto MAU initiated several avoidable investigations for venous thromboembolism.Careful examination elicited amild ascites and a thorough drug history gave recent lowmolecular weight heparin usage. Ultrasoundscan of the abdomen subsequently confirmed the diagnosis of severe OHSS.The d-dimer should therefore be used to negate and notto substantiate a diagnosis of VTE.This case report aims to highlight the importance of OHSS as an uncommon cause of dyspnoeabut whose prevalence is likely to increase in the forthcoming years. We discuss the complications of the misdiagnosis of OHSS, thephysiology behind raised d-dimers, and the potential harm from incorrect treatment or inappropriate imaging.

1. Introduction

Ovarian hyperstimulation syndrome (OHSS) is a well-recognized iatrogenic complication of assisted conceptiontechniques, including in vitro fertilization (IVF) [1]. Althoughthe majority of presentations are mild, severe cases can resultin systemic capillary leakage, causing life-threatening com-plications such as thromboembolic phenomena and multipleorgan dysfunctions [2].

OHSS is common, occurring inmild forms in 33% of IVFcycles and in moderate or severe forms in 3% to 8% of IVFcycles [3]. Although it can occur in all age groups, it is lesscommon in women over the age of 39 years [4]. In the last 10years, in the United States, there has been a 50% increase inthe number of IVF treatments in women over 41 years of age[5]. OHSS is particularly topical following a recent update ofguidelines in the United Kingdom, which extends the age ofthose who can receive treatment to 42 years [6]. This recentincrease in the usage of IVF will inevitably result in a rise inthe number of cases of OHSS seen in the emergency depart-ment (ED). Ultimately, this will give the emergency physicianan important role in expediting and optimizing treatmentfor these patients. On admission to the ED, a plethora of

blood investigations are requested for those who present withacute shortness of breath including complete blood count,urea and electrolytes, troponin, and a d-dimer. The resultsof these investigations need to be interpreted with care asmisinterpretation can lead to serious consequences for thepatient and a delay in treatment.

We report a case of OHSS that was initially misdiagnosedin the ED, attributable to a mildly raised d-dimer, resultingin transfer to the inappropriate specialty and incorrect treat-ment being commenced. We discuss the potential compli-cations for misdiagnosis of OHSS and the pathophysiologybehind the raised d-dimer. This case report highlights animportant message for the emergency physician and raisesawareness of this increasingly common iatrogenic condition.

2. Case Report

A 41-year-old woman, undergoing her second cycle of IVFtreatment, presented to the ED with acute chest pain. Thechest pain was central, was worse on inspiration, and wasnot induced or exacerbated by exercise. The patient hadassociated dyspnea and observations revealed oxygen sat-urations to be 90% on air. Her thrombogenic risk factors

Hindawi Publishing CorporationCase Reports in Emergency MedicineVolume 2015, Article ID 510815, 3 pageshttp://dx.doi.org/10.1155/2015/510815

2 Case Reports in Emergency Medicine

H2O

H2O

H2O

H2O

Pg

Pg

Pg

Pg

Pg

(1) Increased permeability (2)

(3) Clotting cascade

(4) Raised D-dimer

XIIXI

IX

X

Xa

VIII

Plt

Plt PT

Plt FDPD-dimers

Fibrin

FibrinogenThrombin

Hemoconcentration

Figure 1: Schematic illustration of how OHSS causes a rise in d-dimers. Pg = prostaglandin; Plt = platelets; FDP = fibrin degradationproductions; PT= prothrombin. (1) Dotted arrow represents normal blood flow. Prostaglandins are increased inOHSSwhich causes increasedcapillary permeability. This forces water out of the capillaries and into the tissues. (2) Loss of water causes hemoconcentration of the bloodwhich is represented by thick arrows. Due to this, activation of platelets occurs. (3) Activation of platelets causes activation of the clottingcascade (simplified without the activated factors). (4) The final products of the coagulation cascade are fibrin degradation products whichcan be measured in the blood as d-dimers.

included reduced immobility due to back pain and recentIVF [7]. Past medical history included one failed cycle of IVFand a recent embryo implantation in her second IVF cycle.Examination revealed a woman in substantial pain, withassociated tachypnea, tachycardia, and bilateral reduction inair entry to the lung bases.

The presence of thrombogenic risk factors and the clinicalpresentation gave the patient a modified Wells score ofsix, rendering pulmonary embolus a likely diagnosis [8].Consequently, the patient was placed on high flow oxygenand routine bloods, a d-dimer, and a clotting profile wererequested. The d-dimer returned as mildly raised (430mg/L,upper limit of normal in our laboratory was 250mg/L)and the patient was sent to the medical admissions unit(MAU) for further clerking and therapeutic thromboembolictreatment.

In the MAU, two important inconsistencies with theoriginal assessment were established. Firstly, the chest painappeared to be epigastric and was associated with newonset abdominal bloating. Secondly, a thorough drug his-tory highlighted that the patient had been taking a lowmolecular weight heparin following her previous IVF failure.These findings significantly reduced the likelihood of apulmonary embolus. Consequently, beta-human chorionicgonadotropin (beta-hCG) levels and abdominal ultrasoundscan were requested. The beta-hCG returned as raised andthe scan revealed bilateral ovarian enlargement, ascites, and aright-sided pleural effusion, uniting the symptoms and thusconfirming the diagnosis of severe OHSS.

Subsequently, the patient was transferred to gynecologywhere she was closely monitored. During her stay, the ascitesreduced, the shortness of breath improved and the followingweek, she was discharged home with no symptoms.

3. Discussion

This case has illustrated a diagnosis that is important inpatients who are of reproductive age.We have reported a case

of severe OHSS which was mistaken for thromboembolicdisease due to an inadequate history combinedwith a relianceon blood tests that could have potentially led to seriouscomplications.

The complications of OHSS depend on the severity ofthe condition although a misdiagnosis and mistreatmentcan potentially become fatal. Complications from mild casesare usually self-limiting. In the more severe forms, fluidshifts can lead to dehydration resulting in acute kidneyinjury, multiple organ failure, and adult respiratory distresssyndrome. Dehydration also increases the risk of throm-boembolic phenomena and this occurs in 0.7% to 10% ofOHSS patients [9]. Thromboembolic disease is therefore animportant condition to rule out in any potential patient whohas had assisted reproductive technologies (ART). This pro-motes the rationale behind the referral of our patient to theMAU with a suspected pulmonary embolus. However, it alsohighlights the importance of taking a thorough medicationhistory, which revealed that the patient had recently beenstarted on a low-molecular weight heparin in addition tothromboembolic stockings, two factors that reduce the riskof a thromboembolic disease.

In OHSS, the pathophysiology behind the raised d-dimeris thought to be due to an elevation of prostaglandins, whichincrease vascular permeability and result in extravasation offluids into the third space. Extravasation leads to hemocon-centration, which in turn increases serum viscosity and slowsblood flow. The hematological changes increase endothelialadherence of platelets and activate the coagulation cascade.In order to prevent the formation of thrombi, the bodygenerates endogenous hormones to dissolve the fibrin clot.This ultimately increases fibrin degradation products whichare measured as the d-dimer [10]. This whole process isillustrated in Figure 1.

This case imparts an important lesson regarding the inter-pretation of the investigations performed in theED, especiallythe d-dimer.D-dimers are fibrin degradation products, whichhave a high sensitivity but low specificity.They can be elevated

Case Reports in Emergency Medicine 3

in a plethora of conditions including infection, inflammatorydisease, malignancy, OHSS, and pregnancy [11]. In this case,the d-dimer was used to substantiate the diagnosis of athromboembolic disease. Acting on a raised d-dimer is ofparticular significance as radiological investigations, whichare often required for diagnoses of emboli, could be harmfulto both the expectantmother and her fetus [12].This supportsthe use of d-dimers only to rule out a pulmonary embolusand not to substantiate the history and clinical findings.The case also highlights that there is a relationship betweenthromboembolic disease and OHSS and that both conditionsneed to be considered when treated patients have undergoneART.This needs to be highlighted so that vital treatments arenot omitted with potentially life threatening complications.

4. Why Should an Emergency Physician BeAware of This?

Shortness of breath is a common presenting complaint to theED. For this, it is important to considermultiple etiologies forabnormal blood results, especially d-dimers. D-dimer testingis useful only for negating and not substantiating a diagnosisof pulmonary embolism. This case report aims to highlightthe importance of OHSS as an uncommon cause of dyspnea,but whose prevalence is likely to increase in the forthcomingyears as a number of ART procedures are performed.

Conflict of Interests

The authors declare no conflict of interests for this study.

References

[1] R. Klemetti, T. Sevon, M. Gissler, and E. Hemminki, “Compli-cations of IVF and ovulation induction,” Human Reproduction,vol. 20, no. 12, pp. 3293–3300, 2005.

[2] J. A. Stewart, P. J. Hamilton, and A. P. Murdoch, “Thromboem-bolic disease associated with ovarian stimulation and assistedconception techniques,”HumanReproduction, vol. 12, no. 10, pp.2167–2173, 1997.

[3] A. Delvinge and S. Rozenberg, “Epidemiology and preventionof ovarian hyperstimulation syndrome (OHSS): a review,”Human Reproduction Update, vol. 8, no. 6, pp. 559–577, 2002.

[4] L. F. J. M. M. Bancsi, F. J. M. Broekmans, M. J. C. Eijkemans,F. H. de Jong, J. D. F. Habbema, and E. R. Te Velde, “Predictorsof poor ovarian response in in vitro fertilization: a prospectivestudy comparing basal markers of ovarian reserve,” Fertility andSterility, vol. 77, no. 2, pp. 328–336, 2002.

[5] SartCors, “Clinical Summary Report,” 2014, https://www.sart-corsonline.com/.

[6] NICE, Fertility: Assessment and Treatment or People with Fertil-ity Problems. Clinical Guidelines, vol. 156, NICE, 2013.

[7] M. H. Aurousseau, M. M. Samama, A. Belhassen, F. Herve,and J. N. Hugues, “Risk of thromboembolism in relation to anin-vitro fertilization programme: three case reports,” HumanReproduction, vol. 10, no. 1, pp. 94–97, 1995.

[8] P. S. Wells, J. S. Ginsberg, D. R. Anderson et al., “Use of aclinical model for safe management of patients with suspectedpulmonary embolism,”Annals of Internal Medicine, vol. 129, no.12, pp. 997–1005, 1998.

[9] A. Delvigne and S. Rozenberg, “Review of clinical courseand treatment of ovarian hyperstimulation syndrome (OHSS),”Human Reproduction Update, vol. 9, no. 1, pp. 77–96, 2003.

[10] M. M. Alper, L. P. Smith, and E. S. Sills, “Ovarian hyper-stimulation syndrome: current views on pathophysiology, riskfactors, prevention, and management,” Journal of Experimentaland Clinical Assisted Reproduction, vol. 6, article 3, 2009.

[11] G. Y. H. Lip and G. D. Lowe, “Fibrin D-dimer: a useful clinicalmarker of thrombogenesis?” Clinical Science, vol. 89, no. 3, pp.205–214, 1995.

[12] M.Moradi, “Pulmonary thromboembolism in pregnancy: diag-nostic imaging and related consideration,” Journal of Research inMedical Sciences, vol. 18, no. 3, pp. 255–259, 2013.

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